Clinical outcomes of potential high responders after individualized FSH dosing based on anti-Müllerian hormone and body weight.

RESEARCH QUESTION: How does the efficacy and safety of individualized follitropin delta dosing compare with conventional dosing for ovarian stimulation in potential high responders? DESIGN: Retrospective analysis of 153 potential high responders identified on the basis of baseline serum anti-Müllerian hormone (AMH) levels above 35 pmol/l, who were originally randomized to an individualized fixed dose of follitropin delta based on AMH and body weight (n = 78) or to a daily starting dose of 150 IU follitropin alfa (n = 75). RESULTS: At the end of stimulation, patients treated with individualized follitropin delta or conventional follitropin alfa had 12.1 ± 7.0 and 18.3 ± 7.0 (P < 0.001) follicles measuring 12 mm or wider, and 27.3% and 62.7% had serum progesterone levels higher than 3.18 nmol/l (P < 0.001), respectively. Overall number of oocytes in these two respective arms was 9.3 ± 6.7 and 17.9 ± 8.7 (P < 0.001), and the ongoing pregnancy rate per started cycle after fresh blastocyst transfer was 28.2% and 24.0%. The risk of ovarian hyperstimulation syndrome (OHSS) for all cases was three times higher in the conventional follitropin alfa arm at 16.0% versus 5.1% with individualized follitropin delta treatment (P = 0.025) and 26.7% versus 7.7% (P = 0.001) for early moderate or severe OHSS, preventive interventions for early OHSS, or both. CONCLUSIONS: Treatment with individualized follitropin delta provides an improved efficacy-safety balance in women with high ovarian reserve, as it normalizes the ovarian response and decreases the risk of OHSS without compromising the chance of pregnancy.

Individualized follitropin delta dosing reduces OHSS risk in Japanese IVF/ICSI patients: a randomized controlled trial.

RESEARCH QUESTION: This study aimed to establish the efficacy and safety of ovarian stimulation with a follitropin delta individualized fixed-dose regimen based on serum anti-Müllerian hormone (AMH) concentration and body weight versus conventional follitropin beta dosing in Japanese women. DESIGN: This randomized, controlled, assessor-blind, multicentre, non-inferiority trial was conducted in 347 Japanese IVF/intracytoplasmic sperm injection patients. They were randomized to individualized follitropin delta (AMH <15 pmol/l: 12 µg/day; AMH ≥15 pmol/l: 0.10-0.19 µg/kg/day; minimum 6 µg/day; maximum 12 µg/day) or conventional follitropin beta (150 IU/day for the first 5 days, with potential subsequent dose adjustments). The primary end-point was the number of oocytes retrieved with a pre-specified non-inferiority margin (-3.0 oocytes). RESULTS: The primary trial objective was met, as non-inferiority was established for number of oocytes retrieved for individualized follitropin delta dosing compared with conventional follitropin beta dosing (9.3 versus 10.5; lower boundary of 95% confidence interval -2.3). The occurrence of ovarian hyperstimulation syndrome (OHSS) was reduced to approximately half with individualized compared with conventional dosing, with an incidence of 11.2% versus 19.8% (P = 0.021) for OHSS of any grade and 7.1% versus 14.1% (P = 0.027) for moderate/severe OHSS. The live birth rate per started cycle was 23.5% for individualized dosing and 18.6% for conventional dosing. CONCLUSIONS: Dosing with individualized follitropin delta in Japanese women is non-inferior to conventional dosing with follitropin beta for number of oocytes retrieved. The individualized approach shows a favourable benefit-risk profile, providing a statistically significant and clinically relevant reduction in the incidence of OHSS, without compromising live birth rates.

Insulin Resistance and Free Androgen as Predictors for Ovarian Hyperstimulation Syndrome in Non-PCOS Women.

We evaluated the effect of insulin resistance and free androgen index (FAI) in non-PCOS (polycystic ovary syndrome) infertile women following controlled ovarian hyperstimulation. A prospective study was done on 144 infertile non-PCOS women with regular menstrual cycle. At first, insulin resistance (IR), free androgen index (FAI), PCOM (polycystic ovary morphology), AFC (antral follicle count), and AMH (anti-Müllerian hormone) were assessed. The patients underwent assisted reproductive technology (ART), and then preovulatory follicles and oocytes retrieved were recorded. The variables of the study were compared between two groups of patients with ovarian hyperstimulation syndrome (OHSS) (n=66) and non-OHSS patients (n=78). Of the 9 variables: BMI, HOMA-IR, FAI, AFC, AMH, PCOM, and preovulatory follicles were risk factors, while the age and retrieved oocytes were not. The 7 variables that showed significance in the univariate analyses were determined as independent variables included in the multivariable logistic regression analysis, as a result, a total of 5 risk factors, BMI, HOMA-IR, FAI, PCOM, and preovulatory follicles entered the equation. The maximum contribution was HOMA-IR followed by PCOM, FAI, preovulatory follicles and BMI. Patients with OHSS had higher chance to have ovaries with polycystic morphology (74%), about three times more than patients who did not develop OHSS (29%) (p<0.001). The best cut-points for IR, FAI, AFC, AMH, and preovulatry follicles were 2.36, 3.9, 8, 3.3 ng/ml, and 10, respectively. Patients with a higher value of BMI, FAI, HOMA-IR, and preovulatory follicles and the presence of PCOM are more likely to develop OHSS, which are not confined to PCOS patients.

Maternal C-reactive protein and in vitro fertilization (IVF) cycles.

Embryo implantation is accompanied by a potent inflammatory response, and a gradient of cytokines and chemokines produced by endometrial cells supports the embryo-endometrial interaction. C-reactive protein (CRP) serves as an early marker of inflammation and recent studies have illustrated that controlled ovarian hyperstimulation (COH) could increase its levels. Interestingly, a high chance of pregnancy has been reported in women who had an elevated CRP level on the day of embryo transfer. It seems an elevated systemic inflammation in the in vitro fertilization (IVF) cycle can increase the implantation and pregnancy rates. However, the results regarding the association of CRP with ART outcomes are controversial. Therefore, in this review, we aimed to describe how CRP levels change during a cycle of IVF treatment and which factors can potentially affect this pattern of change. Furthermore, the association of CRP with ART outcomes has been discussed.

Plasma pentraxin 3 is higher in early ovarian hyperstimulation syndrome than in uncomplicated in vitro fertilization cycle of high-risk women.

PURPOSE: Pentraxin 3 (PTX3) is a locally secreted, quicker responsive pro-inflammatory protein than C-reactive protein (CRP). We evaluated the value of PTX3 in the prediction of ovarian hyperstimulation syndrome (OHSS), a severe complication of in vitro fertilization (IVF). METHODS: This two-year prospective follow-up study included 27 women with uncomplicated IVF-cycles (IVF group) and 31 patients diagnosed with moderate or severe early OHSS (OHSS group). PTX3 was analysed from follicular fluid (FF) and serial blood samples with enzyme-linked immunoassay and CRP with particle-enhanced immunoturbidimetric assay. The value of PTX3 and CRP in detecting OHSS was examined with receiver operating characteristic (ROC) curve analysis and expressed as the area under the curve (AUC). RESULTS: The circulating PTX3 level peaked at two days after oocyte pick-up (OPU2), and in the OHSS group the level was 1.9 times higher (P = 0.006) than in the IVF group. However, in ROC curve analysis PTX3 (AUC 0.79, best cut off 1.1 µg/L) was not superior to CRP (AUC 0.87; best cut off 9.5 mg/L) in predicting early OHSS. In the IVF group, the FF-PTX3 concentration was 15-20 times higher than in the plasma. PTX3 level at OPU2 correlated with the number of punctured follicles (r = 0.56, n = 22, P = 0.006). Triggering with human chorionic gonadotrophin or early pregnancy had no effect on PTX3 level. CONCLUSION: The elevated PTX3 concentration in OHSS at OPU2, when freeze-all embryos strategy is still possible to consider, indicates that PTX3 level could provide additional benefit in the risk assessment for early OHSS.

Anti-Müllerian Hormone and Its Predictive Utility in Assisted Reproductive Technologies Outcomes.

Anti-Müllerian hormone (AMH) has become one of the most informative biochemical markers of the ovary and is considered the earliest and most sensitive marker of reproductive aging. The accuracy of AMH in predicting ovarian response to controlled ovarian stimulation has led to AMH-based prognostication counseling and individualization of assisted reproductive technology (ART) stimulation protocols to optimize ovarian response and minimize hyperstimulation risks. Although AMH is considered a good predictor of quantitative ART outcomes, its correlation with qualitative ART outcomes is still controversial. The aim of this review is to provide an updated overview of the clinical utility of AMH in predicting ART outcomes.

Ultrasound and hematological changes during early luteal phase in women at high risk for developing ovarian hyperstimulation syndrome.

OBJECTIVE: To assess ultrasound and hematological changes during the early luteal phase following triggering of final oocyte maturation with human chorionic gonadotropin (hCG) in women at high risk for developing ovarian hyperstimulation syndrome (OHSS). METHODS: This was a retrospective cohort study of 319 women undergoing in-vitro fertilization who were at high risk for OHSS following administration of hCG for the triggering of final oocyte maturation. Patients were treated with a gonadotropin-releasing hormone agonist or antagonist protocol and were monitored for 5 days post-oocyte retrieval (early luteal phase). Severe OHSS was diagnosed in the presence of at least moderate ascites and two or more of the following: maximum ovarian diameter (MOD) > 100 mm, hematocrit (Ht) > 45%, white blood cell count (WBC) > 15 000/mm3 , hydrothorax, dyspnea and oliguria. Outcome measures included change in Ht, ascites grade, WBC and MOD, as well as the association between these changes during the early luteal phase. RESULTS: Ascites grade, Ht and WBC increased significantly (P ≤ 0.001) during the early luteal phase, both in patients who developed and in those who did not develop severe early OHSS. MOD increased significantly (P = 0.001) only in patients who developed severe early OHSS. On multivariable analysis, both time following oocyte retrieval and whether severe early OHSS developed were significantly associated with ascites grade, Ht, WBC and MOD; furthermore, there was also a significant interaction between time and development of severe early OHSS for all four variables (P ≤ 0.001). CONCLUSIONS: In women at high risk of OHSS, ascites grade, Ht and WBC significantly increased with time over the 5-day observation period, in line with the pathophysiology of the syndrome. Our data support the use of MOD in the diagnosis of severe early OHSS, and provide novel evidence for the role of change in Ht as a patient-specific hemoconcentration marker during development of OHSS. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Added value today of hormonal measurements in ovarian stimulation in gonadotropin-releasing hormone antagonist treatment cycle.

PURPOSE OF REVIEW: Traditional approach of ovarian stimulation monitoring for in-vitro fertilization involves transvaginal sonography and serum estradiol measurements. Accumulating evidence has shown that hormonal evaluations during ovarian stimulation allow individual cycle optimization, moving away from only predicting the risk of ovarian hyperstimulation syndrome, but in addition assessing the impact of ovarian stimulation on endometrial receptivity, quality of oocytes, and subsequently embryos. The purpose of this review is to discuss the relevance and added value of hormonal monitoring during ovarian stimulation in gonadotropin-releasing hormone antagonist cycles where most of the advances have occurred. RECENT FINDINGS: Basal hormonal status, particularly estradiol, progesterone, and luteinizing hormone are instrumental in prediction of the patients with poor prognosis. Estradiol levels on the day of trigger are less sensitive in predicting ovarian hyperstimulation syndrome then the number of follicles more than 11 mm in diameter. Progesterone elevation on the day of trigger is associated with lower pregnancy rates. The gold standard treatment for progesterone elevation is to adopt a freeze-all strategy when the threshold of 1.50 ng/ml is exceeded. The effect of progesterone elevation on embryo quality remains to be confirmed by more trials. SUMMARY: Endocrine monitoring during ovarian stimulation allows fine-tuning of the physiology of the stimulated cycle and thereby increases the chances of successful treatment outcome.

Association between peak estradiol levels and ovarian torsion among symptomatic patients receiving gonadotropin treatment.

PURPOSE: Ovarian torsion is a surgical emergency that can be clinically challenging to diagnose. Patients who have received assisted reproductive technologies (ART) are a subset of women with an increased risk for torsion. As the ART population continues to increase, there is a need to delineate risk factors for the development of ovarian torsion in this unique population. A pilot study was performed to determine the proportion of patients with suspected ovarian torsion who have received ART and to identify possible diagnostic biomarkers for ovarian torsion among these patients. METHODS: A single institution retrospective cohort study of patients taken to surgery for suspected ovarian torsion over a 5-year period. RESULTS: During the study period, 171 patients were taken to surgery for suspected ovarian torsion. Patients receiving ART constituted 19 (11%) of these patients. Among the 19 fertility treatment patients, 16 had received treatment with gonadotropins, 10 of which had surgically confirmed ovarian torsion. These ten patients had higher preoperative peak estradiol levels (3122 versus 1875 pg/mL, p = 0.05) and a larger ovarian diameter (9.7 versus 7.6 cm, p = 0.05) than the six patients receiving gonadotropins found to not have ovarian torsion. CONCLUSIONS: These results suggest infertility treatment using gonadotropins for ovarian hyperstimulation may be an independent risk factor for ovarian torsion as suggested by the disproportionate number of such individuals represented in the study population (9% of all patients, 84% of fertility patients). Additionally, among women taking gonadotropins, an association exists between peak estradiol levels, ovarian diameter, and risk for ovarian torsion.

The use of ovarian reserve markers in IVF clinical practice: a national consensus.

Ovarian reserve markers have been documented to perform very well in the clinical practice. While this is widely recognized, still now there is no consensus on how to use new biomarkers in the clinical practice. This study was conducted among Italian IVF centres using the Delphi technique, a validated consensus-building process. Briefly three consecutive questionnaires were developed for clinicians in charge of IVF centres. In the first rounds, participants were asked to rate the importance of a list of statements regarding the categorization of ovarian response and the diagnostic role of biomarkers. In round 3, participants were asked to rate their agreement and consensus on the list of statements derived from the first two rounds. There were 120 respondents. Consensus was achieved for many points: (a) poor ovarian response is predicted on the basis of the following: AMH < 1 ng/ml or AFC < 7, FSH ≥ 10 IU/l, age ≥ 40 yrs; (b) hyper-response is predicted on the basis of the following: AMH > 3 ng/ml or AFC > 14; (c) day 3 FSH measurement should always be associated to estradiol; (d) AMH can be measured on a random basis; (e) the measurement of the AFC with the 2D technology may be considered adequate and (f) the AFC should be measured in the early follicular phase and consists in the total number of 2-9 mm follicles in both the ovaries. The present study suggests that extensive consensus on the importance and use of new ovarian reserve markers to improve IVF safety and performance is already present among clinicians.

Predictors of Paracentesis in Women with Severe Ovarian Hyperstimulation Syndrome: A Retrospective Cohort Study.

BACKGROUND: To identify predictors of paracentesis in women with severe ovarian hyperstimulation syndrome (OHSS). METHODS: In a retrospective cohort study, we assessed patient characteristics and outcome measures of women with severe OHSS Golan grade II/III from 1996 to 2010 using univariate and multivariate analyses with the number of paracenteses as the main outcome. RESULTS: Three hundred ninety four women with OHSS Golan grade II (n = 40) and grade III (n = 354) were included in the study. Paracentesis was performed in 108/394 (27%) of these women. One paracentesis was performed in 63 (16%), 2 paracenteses in 26 (6%), and ≥3 paracenteses 19 (5%) women, respectively. No thrombotic or cerebrovascular morbidity occurred. The mortality of the cohort was 0/394 (0%). In a univariate analysis, late onset OHSS (p = 0.02), pregnancy (p < 0.001), human chorionic gonadotropin use (p = 0.02), ovarian diameter (p = 0.006), and elevated serum levels of alanine aminotransferase (p < 0.001), hematocrit (p < 0.001), leucocytes (p < 0.001), thrombocytes (p < 0.001), and uric acid (p < 0.001) were associated with paracentesis. In a multivariate logistic regression analysis, only alanine aminotransferase (OR 1.006; 95% CI 1.001-1.01) and hematocrit (OR 1.16; 95% CI 1.05-1.27) were independently associated with paracentesis. CONCLUSION: Alanine aminotransferase and hematocrit at initial presentation are independent predictors of paracentesis.

Role of serum miRNAs in the prediction of ovarian hyperstimulation syndrome in polycystic ovarian syndrome patients.

BACKGROUND: Polycystic ovarian syndrome (PCOS) causes a significantly increased risk of ovarian hyperstimulation syndrome (OHSS). Here, we focused on the altered expression of serum miRNAs and their predictive value for OHSS in PCOS patients. METHODS: We used the TaqMan low density array followed by individual quantitative reverse transcription-polymerase chain reaction to identify and validate the expression of serum miRNAs in PCOS patients likely to develop severe OHSS. RESULTS: The miR-16 and miR-223 expression levels were significantly reduced in the patients who were likely to develop severe OHSS than in the control subjects who were likely to develop mild or no OHSS. The sensitivity and specificity of the basal LH, basal LH/FSH, and body mass index (BMI) as OHSS predictors were also evaluated. miR-16 was the most efficient for OHSS prediction as it yielded the highest AUC. Logistic binary regression analyses revealed a positive association of miR-223 and BMI. CONCLUSION: Serum miRNAs are differentially expressed in PCOS patients likely to suffer from severe OHSS. We identified and validated two serum miRNAs that have potential for use as novel noninvasive biomarkers to accurately predict OHSS before controlled ovarian hyperstimulation (COH) for PCOS patients.

The Ser680Asn polymorphism in the follicle-stimulating hormone receptor gene is associated with the ovarian response in controlled ovarian hyperstimulation.

OBJECTIVE: Polymorphisms in the follicle-stimulating hormone receptor (FSHR) gene are reported to be associated with the ovarian response in controlled ovarian hyperstimulation (COH), although there remains some discordance between studies. Here, using the largest patient sample to date, we evaluated the association of the p.Ser680Asn (S(680)N) polymorphism in the FSHR gene with the outcome of COH. DESIGN: Cohort study. SETTING: Medical academy and hospital. PATIENTS: A total of 1250 infertile Chinese women undergoing IVF/ICIS-ET treatment were included. MEASURES: The association between an FSHR polymorphism (S(680)N) and the ovarian response was analysed. Genotyping was performed by utilizing direct sequencing and the Sequenom MassARRAY iPLEX platform. Follicular fluid oestradiol (E2) and follicle-stimulating hormone (FSH) concentrations were determined using electrochemiluminesence immunoassays. The ovarian response parameters were analysed based on the FSHR genotypes. The odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated for the risk genotypes and alleles. RESULTS: There were linear correlations between the basal FSH level, exogenous gonadotropin consumption, and oocytes retrieved and the Ser680 alleles. Patients in the homozygous SS group demonstrated higher basal FSH levels, required more dosage of exogenous gonadotropin for ovarian stimulation, and had fewer numbers of oocytes retrieved compared with patients in the homozygous NN and heterozygous groups. Logistic regression analysis revealed that the OR of a poor ovarian response for the NS genotype was 1·79 (95% CI 1·28-2·61; P < 0·001), whereas that for the SS genotype was 2·25 (95% CI 1·40-3·58; P < 0·001) after adjusting for age, BMI and basal FSH level. The concentration of E2 in the follicular fluid was significantly higher in subjects with the NN genotype than the SS genotype (772 ± 545 ng/ml vs. 1299 ± 504 ng/ml). CONCLUSIONS: Follicle-stimulating hormone receptor gene polymorphism at position 680 is associated with different ovarian responses to controlled ovarian hyperstimulation.

Serum anti-Mullerian hormone assessment of ovarian reserve and polycystic ovary syndrome status over the reproductive lifespan.

BACKGROUND: To determine normal ranges for serum anti-Mullerian hormone (AMH) using the new automated Elecsys AMH assay platform, with a view to establishing values that signify premature loss of ovarian reserve, increased risk for an excessive response during IVF stimulation and a likely diagnosis of polycystic ovary syndrome (PCOS). MATERIALS AND METHODS: Serum AMH was measured by the Elecsys automated electrochemiluminescence assay in 654 women undergoing gynaecological assessment. RESULTS: Serum AMH levels peaked before 25 years of age, with mean AMH levels halving by 36 and falling to a quarter of their peak by 40 years of age. Overall, AMH results of 95% of patients with PCOS exceeded the 50th percentile for their age, with 72.1% having an AMH result in the top quartile for age. ROC analysis suggested that a serum AMH ≥36 pmol L(-1) is the best determinant of PCOS status (sensitivity 83.7% and specificity 82.3%). Serum AMH exhibited an excellent correlation with ultrasound-assessed antral follicle count (AFC) (r = 0.836, P < 0.0001), with a result of 20 pmol L(-1) corresponding to an AFC of 16 and, therefore, increased risk of ovarian hyperstimulation syndrome (OHSS) during IVF treatment. CONCLUSION: Serum AMH is a sensitive marker of age-related decline in ovarian reserve status. A serum AMH result >36 pmol L(-1) , or above the 75th percentile for age, is highly suggestive of a diagnosis of PCOS. A serum AMH result below the 10th percentile for age suggests accelerated loss of ovarian reserve, while an AMH result exceeding 20 pmol L(-1) suggests an increased risk of OHSS during IVF treatment.

Investigation of short- and long-term effects of ovarian hyperstimulation syndrome on ovarian reserve: an experimental study.

PURPOSE: To investigate the short and long-term effects of ovarian hyperstimulation syndrome (OHSS) on serum levels of vascular endothelial growth factor (VEGF) and endothelin-1 and ovarian follicular reserve (OFR). MATERIALS AND METHODS: An experimental case-control study was conducted on a university animal laboratory with 20 immature (22-day-old) virgin female Wistar Albino rats. Firstly, rats were divided into two groups. Group 1 (n = 10): control and Group 2 (n = 10): experimental OHSS induced rats. Secondly, Group 2 was randomly divided into two groups on the day of OHSS development (27th day) as follows: Group 3 (n = 5): 27-day-old OHSS induced rats and Group 4 (n = 5): 27-day-old OHSS induced rats supervised for seven days. Group 1 was divided into two groups to constitute age-matched controls as follows: Group 5 (n = 5): 27-day-old rats, Group 6 (n = 5): 35-day-old rats. The comparisons of Group 3 vs Group 5 and Group 4 vs Group 6 were performed. Main outcome measures were OFR, serum levels of VEGF, and endothelin-1. RESULTS: While the OFR and primordial follicle number (PFN) of Group 3 were significantly lower than those of Group 5 (p < 0.05); VEGF and endothelin-1 levels and atretic follicle number (AFN) were significantly higher in Group 3 compared to Group 5 (p < 0.05). In Group 4, PFN was significantly lower (p < 0.05) and AFN was significantly (p < 0.05) higher than Group 6. However, there were no statistically significant difference between Group 4 and Group 6 regarding the parameters of OFR, serum levels of VEGF, and endothelin-1. CONCLUSION: This experimental OHSS model revealed increased serum VEGF and endothelin-1 levels and decreased OFR during short-term of OHSS. OHSS showed detrimental effect on PFN of rats during long-term.

Kinase insert domain receptor/vascular endothelial growth factor receptor 2 (KDR) genetic variation is associated with ovarian hyperstimulation syndrome.

BACKGROUND: The objective of this investigation was to determine if kinase insert domain/vascular endothelial growth factor receptor 2 (KDR/VEGFR2) genetic variation was associated with the development of ovarian hyperstimulation syndrome (OHSS) in patients undergoing controlled ovarian hyperstimulation (COH). METHODS: This was a case-control study of 174 patients who underwent controlled ovarian stimulation. Patient blood samples were genotyped for single nucleotide polymorphisms (SNPs) spanning the KDR locus. OHSS development, clinical outcome variables, SNP and haplotype frequencies were compared between control (n = 155) and OHSS (n = 19) groups. RESULTS: Patients who developed OHSS had significantly higher response markers (estradiol levels of the day of hCG administration, number of follicles developed, number of eggs retrieved) than control patients. When adjusted for age and self-identified race, the rs2305945 G/T genotype was associated (P = 0.027) with a decreased risk (OR = 0.30; 95% CI = 0.10, 0.93) of developing OHSS using an overdominant model. The rs2305945 G/T variant was also associated with decreased COH response (number of follicles, number of eggs retrieved) in an overdominant model. The rs2305948, rs1870378, rs2305945 (C-T-G) haplotype was associated with both decreased COH response and OHSS risk (unadjusted OR = 0.10; 95% CI = 0.01, 0.80, P = 0.031). CONCLUSIONS: The KDR receptor is believed to play a central role OHSS development and is a target for pharmacological prevention of OHSS. These results indicate that genetic variation in the KDR gene may impact individual risk of developing OHSS from COH. In addition, the rs2305948 SNP and C-T-G haplotype might serve as potential biomarkers for poor ovarian response to COH.

Hyperstimulation syndrome: the levels of inhibin A and B in sera and follicular fluids.

Ovarial hyperstimulation syndrome (OHSS) represents a serious problem encountered during in vitro fertilization (IVF). We examined 10 patients with OHSS and 50 women also hormonally stimulated in the process of IVF who had no complications. In all women, we evaluated the number of obtained oocytes and the level of inhibins A and B in sera and follicular fluid collected at the time of ovarial puncture, the day embryo transfer and on the day of positivity for hCG. The level of inhibin B in both fluids was significantly higher (t = 0.0403) in women with high quality of oocytes. The higher level of inhibin A was detected in patients with OHSS at the time of oocyte collection and on the day of embryo transfer. Inhibin B was elevated only at the time of oocyte collection. The levels of inhibin A and B were identical in follicular fluids collected from both ovaries. We observed no statistically significant differences between the levels of inhibin A and B in follicular fluids of women in the absence of OHSS. Evaluation of serum levels of inhibin A and B at the time of oocyte collection may contribute to the prognosis and prevention of OHSS.

Relationship between human chorionic gonadotropin serum levels and the risk of ovarian hyperstimulation syndrome.

The object of this retrospective cohort study was to determine if hCG levels correlate with ovarian hyperstimulation syndrome (OHSS) risk after adjustment for other risk factors during in vitro fertilization (IVF). We measured serum hCG approximately 12 h after hCG trigger in women undergoing 406 cycles of controlled ovarian hyperstimulation for IVF between June 2006 and December 2009. Serum hCG levels were measured 12 h after trigger. Bivariate logistic regression was used to assess the association between patient and cycle characteristics and OHSS. In our series, mild to moderate OHSS occurred in 9% (38/406), and severe OHSS diagnosed in 1.5% (6/406) of IVF cycles. OHSS risk was increased in younger women (<30 years old: adjusted odds ratio: aOR 2.46, 95% confidence interval: CI 1.14-5.34), increased number of oocytes (11-20: aOR 6.79, 95% CI 1.97-23.40; >20: aOR 17.55, 95% CI 4.84-63.70), and increase E2 levels (≥3,000 pg/mL: aOR 2.59, 95% CI 1.33-5.05), but was unrelated to hCG level (100-200 IU/L: aOR 1.53, 95% CI 0.60-3.91; ≥200 IU/L: aOR 1.42 95% CI 0.48-4.20). These results indicate that OHSS risk during IVF is unrelated to serum hCG level measured approximately 12 h after trigger.

The rate of high ovarian response in women identified at risk by a high serum AMH level is influenced by the type of gonadotropin.

The aim was to compare ovarian response and clinical outcome of potential high-responders after stimulation with highly purified menotropin (HP-hMG) or recombinant follicle-stimulating hormone (rFSH) for in vitro fertilisation/intracytoplasmic sperm injection. Retrospective analysis was performed on data collected in two randomized controlled trials, one conducted following a long GnRH agonist protocol and the other with an antagonist protocol. Potential high-responders (n = 155 and n = 188 in the agonist and antagonist protocol, respectively) were defined as having an initial anti-Müllerian hormone (AMH) value >75th percentile (5.2 ng/ml). In both protocols, HP-hMG stimulation in women in the high AMH category was associated with a significantly lower occurrence of high response (≥15 oocytes retrieved) than rFSH stimulation; 33% versus 51% (p = 0.025) and 31% versus 49% (p = 0.015) in the long agonist and antagonist protocol, respectively. In the potential high-responder women, trends for improved live birth rate were observed with HP-hMG compared with rFSH (long agonist protocol: 33% versus 20%, p = 0.074; antagonist protocol: 34% versus 23%, p = 0.075; overall population: 34% versus 22%, p = 0.012). In conclusion, the type of gonadotropin used for ovarian stimulation influences high-response rates and potentially clinical outcome in women identified as potential high-responders.

Gonadotroph adenoma causing ovarian hyperstimulation syndrome in a premenopausal woman.

INTRODUCTION: Gonadotroph adenomas occur commonly in middle-aged adults without any specific endocrinological symptoms. To date, only 30 cases of gonadotropinoma causing ovarian hyperstimulation syndrome in pre-menopausal women have been reported. CASE REPORT: A 37-year old woman with pituitary macroadenoma and hyperprolactinaemia was admitted to the Department of Endocrinology, Diabetology and Isotope Therapy. She presented with recurrent ovarian cysts, menstrual disturbances, headaches, visual impairment and galactorrhea. Her endocrine profile showed normal values of FSH, elevated concentrations of estradiol and suppressed LH levels. Transsphenoidal resection of the tumor tissue resulted in normalization of the hormone values and improvement in the clinical picture. CONCLUSIONS: Gonadotroph adenomas should be considered in the differential diagnosis in premenopausal women with OHSS.